scholarly journals DNA methylation of blood cells is associated with prevalent type 2 diabetes in a meta-analysis of four European cohorts

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Diana L. Juvinao-Quintero ◽  
Riccardo E. Marioni ◽  
Carolina Ochoa-Rosales ◽  
Tom C. Russ ◽  
Ian J. Deary ◽  
...  

Abstract Background Type 2 diabetes (T2D) is a heterogeneous disease with well-known genetic and environmental risk factors contributing to its prevalence. Epigenetic mechanisms related to changes in DNA methylation (DNAm), may also contribute to T2D risk, but larger studies are required to discover novel markers, and to confirm existing ones. Results We performed a large meta-analysis of individual epigenome-wide association studies (EWAS) of prevalent T2D conducted in four European studies using peripheral blood DNAm. Analysis of differentially methylated regions (DMR) was also undertaken, based on the meta-analysis results. We found three novel CpGs associated with prevalent T2D in Europeans at cg00144180 (HDAC4), cg16765088 (near SYNM) and cg24704287 (near MIR23A) and confirmed three CpGs previously identified (mapping to TXNIP, ABCG1 and CPT1A). We also identified 77 T2D associated DMRs, most of them hypomethylated in T2D cases versus controls. In adjusted regressions among diabetic-free participants in ALSPAC, we found that all six CpGs identified in the meta-EWAS were associated with white cell-types. We estimated that these six CpGs captured 11% of the variation in T2D, which was similar to the variation explained by the model including only the common risk factors of BMI, sex, age and smoking (R2 = 10.6%). Conclusions This study identifies novel loci associated with T2D in Europeans. We also demonstrate associations of the same loci with other traits. Future studies should investigate if our findings are generalizable in non-European populations, and potential roles of these epigenetic markers in T2D etiology or in determining long term consequences of T2D.

2014 ◽  
Vol 111 (12) ◽  
pp. 2047-2058 ◽  
Author(s):  
Lukas Schwingshackl ◽  
Georg Hoffmann

The aim of the present systematic review and meta-analysis was to examine the long-term effects ( ≥ 12 months) of high-fat (HF) v. low-fat (LF) diet consumption on the indicators of glycaemic control as well as cardiovascular risk factors in pre-diabetic and diabetic individuals. Literature search was carried out using the electronic databases MEDLINE, Embase and the Cochrane Trial Register until November 2013. Study-specific weighted mean differences (MD) were pooled using a random-effects model of the Cochrane software package Review Manager 5.1 and Stata 12.0 was used for meta-regressions. A total of fourteen trials met the inclusion criteria and a maximum of 1753 subjects were included in the meta-analysis. HF regimens were found to result in a significant decrease in TAG levels (MD − 0·19 mmol/l, 95 % CI − 0·23, − 0·14, P< 0·001; I2= 0 %, P= 0·58) and diastolic blood pressure (MD − 1·30 mmHg, 95 % CI − 1·73, − 0·87, P< 0·001; I2= 0 %, P= 0·60) and a significant increase in HDL-cholesterol levels (MD 0·05 mmol/l, 95 % CI 0·01, 0·08, P= 0·01; I2= 57 %, P= 0·01). In addition, MD in the reductions of fasting glucose levels ( − 0·41 mmol/l, 95 % CI − 0·74, − 0·08, P= 0·01; I2= 56 %, P= 0·02) were significantly high in patients with type 2 diabetes adhering to a HF diet. HF and LF diets might not be of equal value in the management of either pre-diabetes or type 2 diabetes, leading to emphasis being placed on the recommendations of HF diets.


2021 ◽  
Author(s):  
Minako Imamura ◽  
Atsushi Takahashi ◽  
Masatoshi Matsunami ◽  
Momoko Horikoshi ◽  
Minoru Iwata ◽  
...  

Abstract Several reports have suggested that genetic susceptibility contributes to the development and progression of diabetic retinopathy. We aimed to identify genetic loci that confer susceptibility to diabetic retinopathy in Japanese patients with type 2 diabetes. We analysed 5 790 508 single nucleotide polymorphisms (SNPs) in 8880 Japanese patients with type 2 diabetes, 4839 retinopathy cases and 4041 controls, as well as 2217 independent Japanese patients with type 2 diabetes, 693 retinopathy cases, and 1524 controls. The results of these two genome-wide association studies (GWAS) were combined with an inverse variance meta-analysis (Stage-1), followed by de novo genotyping for the candidate SNP loci (p &lt; 1.0 × 10−4) in an independent case–control study (Stage-2, 2260 cases and 723 controls). After combining the association data (Stage-1 and -2) using meta-analysis, the associations of two loci reached a genome-wide significance level: rs12630354 near STT3B on chromosome 3, p = 1.62 × 10−9, odds ratio (OR) = 1.17, 95% confidence interval (CI) 1.11–1.23, and rs140508424 within PALM2 on chromosome 9, p = 4.19 × 10−8, OR = 1.61, 95% CI 1.36–1.91. However, the association of these two loci were not replicated in Korean, European, or African American populations. Gene-based analysis using Stage-1 GWAS data identified a gene-level association of EHD3 with susceptibility to diabetic retinopathy (p = 2.17 × 10−6). In conclusion, we identified two novel SNP loci, STT3B and PALM2, and a novel gene, EHD3, that confers susceptibility to diabetic retinopathy; however, further replication studies are required to validate these associations.


2020 ◽  
Author(s):  
Xiaobo LIU ◽  
Chao Dong ◽  
Hong Jiang ◽  
Dongling Zhong ◽  
Yuxi Li ◽  
...  

Abstract Background: The prevalence of type 2 diabetes mellitus (T2DM) is growing in China. Both physical and psychological complications occur along with the development of T2DM. The patients with depression account for a significant proportion of T2DM. Depressive symptoms interfere with blood glucose management, leading to poorer treatment outcome and even relate to the occurrence of other serious complications of T2DM population. Among these T2DM patients with depression, early detection and treatment is essential and effective. Knowledge of the current prevalence of depression in T2DM patients as well as associated risk factors may be meaningful for healthcare planning. Therefore, we plan to conduct a systematic review and meta-analysis to evaluate the Chinese prevalence of depression in T2DM and explore associated risk factors.Methods: We will search literatures recorded in MEDLINE/PubMed, EMBASE, the Cochrane Library, Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), Chinese Science and Technology Periodical Database (VIP), and Wanfang database (Wanfang Data). The grey literatures and reference list will be manually searched. We will include population-based, cross-sectional surveys that investigated the Chinese prevalence of depression in T2DM or/and researched the possible risk factors. Two reviewers will screen studies, extract data and evaluate quality independently. We will assess inter-rater agreement between reviewers for study inclusion, data extraction, and study quality assessment using Kappa statistics. The primary outcome will be the pooled Chinese prevalence of depression in T2DM patients. The secondary outcome will contain the potential risk factors for depression in patients with T2DM. R software (version 3.6.1) and STATA software (version 12) will be used for data analysis.Discussion: This systematic review will provide comprehensive evidence of the Chinese prevalence and risk factors of depression in patients with T2DM. we expect to provide evidence basis for healthcare practitioners and policy makers to pay attention to the mental health of T2DM. Our data will highlight the need and importance of early detection and intervention for depression in patients with T2DM. Systematic review registration: PROSPERO CRD42020182979.


Author(s):  
Debby Syahru Romadlon ◽  
Faizul Hasan ◽  
Bayu Satria Wiratama ◽  
Hsiao‐Yean Chiu

2010 ◽  
Vol 163 (3) ◽  
pp. 427-434 ◽  
Author(s):  
José Miguel Dora ◽  
Walter Escouto Machado ◽  
Jakeline Rheinheimer ◽  
Daisy Crispim ◽  
Ana Luiza Maia

ObjectiveThe type 2 deiodinase (D2) is a key enzyme for intracellular triiodothyronine (T3) generation. A single-nucleotide polymorphism in D2 (Thr92Ala) has been associated with increased insulin resistance in nondiabetic and type 2 diabetes (DM2) subjects. Our aim was to evaluate whether the D2 Thr92Ala polymorphism is associated with increased risk for DM2.Design and methodsA case–control study with 1057 DM2 and 516 nondiabetic subjects was performed. All participants underwent genotyping of the D2 Thr92Ala polymorphism. Additionally, systematic review and meta-analysis of the literature for genetic association studies of D2 Thr92Ala polymorphism and DM2 were performed in Medline, Embase, LiLacs, and SciELO, and major meeting databases using the terms ‘rs225014’ odds ratio (OR) ‘thr92ala’ OR ‘T92A’ OR ‘dio2 a/g’.ResultsIn the case–control study, the frequencies of D2 Ala92Ala homozygous were 16.4% (n=173) versus 12.0% (n=62) in DM2 versus controls respectively resulting in an adjusted OR of 1.41 (95% confidence intervals (CI) 1.03–1.94, P=0.03). The literature search identified three studies that analyzed the association of the D2 Thr92Ala polymorphism with DM2, with the following effect estimates: Mentuccia (OR 1.40 (95% CI 0.78–2.51)), Grarup (OR 1.09 (95% CI 0.92–1.29)), and Maia (OR 1.22 (95% CI 0.78–1.92)). The pooled effect of the four studies resulted in an OR 1.18 (95% CI 1.03–1.36, P=0.02).ConclusionsOur results indicate that in a case–control study, the homozygosity for D2 Thr92Ala polymorphism is associated with increased risk for DM2. These results were confirmed by a meta-analysis including 11 033 individuals, and support a role for intracellular T3 concentration in skeletal muscle on DM2 pathogenesis.


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